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Pharmacological research

Pharmacological research

IF: 9.1
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Celastrol inhibits lung cancer growth by triggering histone acetylation and acting synergically with HDAC inhibitors.

Published:1 November 2022 DOI: 10.1016/j.phrs.2022.106487 PMID: 36202184
Geer Chen , Xiaoyu Zhu , Jiaqi Li, Yao Zhang, Xiaoxuan Wang, Ren Zhang, Xinchen Qin, Xi Chen, Junyi Wang, Weilin Liao, Zongjin Wu, Lu Lu, Weiyu Wu, Haijie Yu, Lijuan Ma

Abstract

Alterations in histone modification have been linked to cancer development and progression. Celastrol, a Chinese herbal compound, shows potent anti-tumor effects through multiple signaling pathways. However, the involvement of histone modifications in this process has not yet been illustrated. In this study, barcode sequencing of a eukaryotic genome-wide deletion library revealed that histone modifications, especially histone acetylation associated with the NuA4 histone acetyltransferase complex, were involved in the anti-proliferation actions of celastrol. The essential roles of histone modification were verified by celastrol sensitivity tests in cells lacking specific genes, such as genes encoding the subunits of the NuA4 and Swr1 complex. The combination of celastrol and histone deacetylase inhibitors (HDACi), rather than the combination of celastrol and histone acetyltransferase inhibitors, synergistically suppressed cancer cell proliferation. In addition to upregulating H4K16 acetylation (H4K16ac), celastrol regulates H3K4 tri-methylation and H3S10 phosphorylation. Celastrol treatment significantly enhanced the suppressive effects of HDACi on lung cancer cell allografts in mice, with significant H4K16ac upregulation, indicating that a combination of celastrol and HDACi is a potential novel therapeutic approach for patients with lung cancer.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
TNU9056 1450644-28-6 C6H4N2S4 43 suppliers $29.00-$1160.00
TNU9056 1450644-28-6 C6H4N2S4 43 suppliers $29.00-$1160.00
TNU9056 1450644-28-6 C6H4N2S4 43 suppliers $29.00-$1160.00
TNU9056 1450644-28-6 C6H4N2S4 43 suppliers $29.00-$1160.00

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